MiR-152 May Silence Translation of CaMK II and Induce Spontaneous Immune Tolerance in Mouse Liver Transplantation

• DOI: 10.1371/journal.pone.0105096
• Publication Date: 2014-08-18T19:32:30Z
• Authors: Yan Wang; Yang Tian; Yuan Ding; Jingcheng Wang; Sheng Yan; Lin Zhou; Haiyang Xie; Hui Chen; Hui Li; Jinhua Zhang; Jiacong Zhao; Shusen Zheng
• Keywords: Male; 0303 health sciences; Reverse Transcriptase Polymerase Chain Reaction; Science; Q; Blotting, Western; R; Liver Transplantation; Mice, Inbred C57BL; Mice; MicroRNAs; 03 medical and health sciences; Immune Tolerance; Medicine; Animals; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Research Article; Oligonucleotide Array Sequence Analysis

Spontaneous immune tolerance in mouse liver transplantation has always been a hotspot in transplantation-immune research. Recent studies revealed that regulatory T cells (Tregs), hepatic satellite cells and Kupffer cells play a potential role in spontaneous immune tolerance, however the precise mechanism of spontaneous immune tolerance is still undefined. By using Microarray Chips, we investigated different immune regulatory factors to decipher critical mechanisms of spontaneous tolerance after mouse liver transplantation. Allogeneic (C57BL/6-C3H) and syngeneic (C3H-C3H) liver transplantation were performed by 6-8 weeks old male C57BL/6 and C3H mice. Graft samples (N = 4 each group) were collected from 8 weeks post-operation mice. 11 differentially expressed miRNAs in allogeneic grafts (Allografts) vs. syngeneic grafts (Syngrafts) were identified using Agilent Mouse miRNA Chips. It was revealed that 185 genes were modified by the 11 miRNAs, furthermore, within the 185 target genes, 11 of them were tightly correlated with immune regulation after Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and Genbank data cross-comparison. Verified by real-time PCR and western blot, our results indicated that mRNA expression levels of IL-6 and TAB2 were respectively down regulated following miR-142-3p and miR-155 augment. In addition, increased miR-152 just silenced mRNA of CaMK II and down-regulated translation of CaMK II in tolerated liver grafts, which may play a critical role in immune regulation and spontaneous tolerance induction of mouse liver transplantation.